Stroke is a major public health problem in the United States, where it is the 5th leading cause of death and the leading cause of adult disability. Therefore, there is great need for translational and clinical research to develop interventions that prevent, treat, or enhance recovery after stroke. However, clinical trials require significant infrastructure, and the time and energy required to assemble this infrastructure for individual trials is a major barrier to progress. The NINDS StrokeNet was established in 2013 as a national stroke trials infrastructure, designed to maximize efficiencies by centralizing regulatory, IRB approval, and contractual agreements. With a single National Clinical Coordinating Center (NCC), a single National Data Management Center (DMC), and 25 Regional Coordinating Centers (RCCs) throughout the US, StrokeNet was established to efficiently recruit and enroll patients for stroke trials. The Midwestern states of Missouri (MO) and Kansas (KS) were not represented in the prior cycle of StrokeNet. Yet Missouri ranks 4th in stroke prevalence3 and 9th in stroke mortality4, among all states in the US, and Kansas is not far behind. Here we forward a proposal to develop the Mid-America Regional Coordinating Center (MARCC) at Washington University School of Medicine and affiliated Barnes-Jewish Hospital, in collaboration with three other high-volume tertiary care Stroke Centers spanning the midwestern states of MO, KS, and IL: St. Luke?s Hospital in Kansas City, MO; St. Louis University Hospital (SLU) in St. Louis, MO; and the Order of St. Francis Medical Center in Peoria, IL. Each of these medical centers is a tertiary care hub with large networks of referring hospitals, and have extensive experience participating in multi-center stroke trials. Thus, MARCC is a ?Network of Networks.? Drawing from both rural and urban settings, the hospitals of MARCC admit almost 5,000 stroke patients per year, including patients from diverse racial backgrounds and socioeconomic strata. Moreover, the collective group of stroke clinicians, investigators, and scientists that will participate in MARCC have diverse expertise that will permit the implementation of stroke trials across the translational and treatment spectrum. We propose to establish MARCC as one of the 25 RCCs with the following specific aims: Aim 1. To establish and maintain a seamless tri-state stroke trials infrastructure?the Mid-America Regional Coordinating Center (MARCC). Aim 2. To effectively and efficiently conduct NINDS StrokeNet trials of stroke prevention, treatment and recovery through the MARCC. Aim 3. To recruit and train future clinician- scientists in stroke research through fellowship training and career enhancement.